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Article

Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine‑disrupting chemicals

  • Authors:
    • Pei‑Jing Yang
    • Ming‑Feng Hou
    • Eing‑Mei Tsai
    • Shih‑Shin Liang
    • Chien‑Chih Chiu
    • Fu Ou‑Yang
    • Jung‑Yu Kan
    • Chiung‑Yu Peng
    • Tsu‑Nai Wang
  • View Affiliations / Copyright

    Affiliations: Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan, R.O.C.
  • Pages: 2766-2777
    |
    Published online on: August 30, 2018
       https://doi.org/10.3892/or.2018.6675
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Abstract

A disintegrin and metalloproteinase domain 33 (ADAM33) gene is a transmembrane glycoprotein that mediates changes in cell adhesion and plays an important role in cancer progression. Since bisphenol A (BPA) and phthalates are epigenetically toxic, the purpose of this study was to examine whether BPA and phthalate metabolites, including monoethyl phthalate (MEP), mono‑n‑butyl phthalate (MBP), mono‑isobutyl phthalate (MIBP), mono(2‑ethylhexyl) phthalate (MEHP), mono(2‑ethyl‑5‑hydroxyhexyl) phthalate (MEHHP), mono(2‑ethyl‑5‑carboxypentyl) phthalate (MECPP), and mono(2‑ethyl‑5‑oxohexyl) phthalate (MEOHP), have an epigenetic impact on ADAM33 and the incidence of breast cancer. CpG islands of breast cancer microarray datasets obtained from the Gene Expression Omnibus (GEO) were used to assess the ADAM33 methylation profile. We designed a case‑control study including 44 cases and 22 age‑matched controls to detect the methylation status of intron 1 in ADAM33 from peripheral blood mononuclear cells (PBMCs) in blood, using BSP, nested PCR, and bisulfite sequencing, and measured the in vivo gene expression of ADAM33 and the urinary concentrations of endocrine‑disrupting chemicals (EDCs), using real‑time PCR, high‑performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC‑MS). Only one dataset, GSE32393, reached significance (P=0.016). ADAM33 expression and methylation frequencies at CpG site 3 in intron 1 were higher in the control group. We found a positive association between intron 1 methylation level and ADAM33 expression as well as urinary concentrations of MEHHP, MECPP, MEOHP and Σ4MEHP (the sum of MEHP, MECPP, MEHHP, and MEOHP) in the cases. This study suggests that metabolites of phthalate such as MEHHP, MECPP, MEOHP and Σ4MEHP may increase the intron 1 methylation level to elevate ADAM33 gene expression and have a protective effect on reducing the risk of breast cancer.
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Spandidos Publications style
Yang PJ, Hou MF, Tsai EM, Liang SS, Chiu CC, Ou‑Yang F, Kan JY, Peng CY and Wang TN: Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine‑disrupting chemicals. Oncol Rep 40: 2766-2777, 2018.
APA
Yang, P., Hou, M., Tsai, E., Liang, S., Chiu, C., Ou‑Yang, F. ... Wang, T. (2018). Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine‑disrupting chemicals. Oncology Reports, 40, 2766-2777. https://doi.org/10.3892/or.2018.6675
MLA
Yang, P., Hou, M., Tsai, E., Liang, S., Chiu, C., Ou‑Yang, F., Kan, J., Peng, C., Wang, T."Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine‑disrupting chemicals". Oncology Reports 40.5 (2018): 2766-2777.
Chicago
Yang, P., Hou, M., Tsai, E., Liang, S., Chiu, C., Ou‑Yang, F., Kan, J., Peng, C., Wang, T."Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine‑disrupting chemicals". Oncology Reports 40, no. 5 (2018): 2766-2777. https://doi.org/10.3892/or.2018.6675
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Spandidos Publications style
Yang PJ, Hou MF, Tsai EM, Liang SS, Chiu CC, Ou‑Yang F, Kan JY, Peng CY and Wang TN: Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine‑disrupting chemicals. Oncol Rep 40: 2766-2777, 2018.
APA
Yang, P., Hou, M., Tsai, E., Liang, S., Chiu, C., Ou‑Yang, F. ... Wang, T. (2018). Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine‑disrupting chemicals. Oncology Reports, 40, 2766-2777. https://doi.org/10.3892/or.2018.6675
MLA
Yang, P., Hou, M., Tsai, E., Liang, S., Chiu, C., Ou‑Yang, F., Kan, J., Peng, C., Wang, T."Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine‑disrupting chemicals". Oncology Reports 40.5 (2018): 2766-2777.
Chicago
Yang, P., Hou, M., Tsai, E., Liang, S., Chiu, C., Ou‑Yang, F., Kan, J., Peng, C., Wang, T."Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine‑disrupting chemicals". Oncology Reports 40, no. 5 (2018): 2766-2777. https://doi.org/10.3892/or.2018.6675
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